PROPOSED STRUCTURE OF PUTATIVE GLUCOSE CHANNEL IN GLUT1 FACILITATIVE GLUCOSE-TRANSPORTER

A family of structurally related intrinsic membrane proteins (facilita tive glucose transporters) catalyzes the movement of glucose across th e plasma membrane of animal cells. Evidence indicates that these prote ins show a common structural motif where approximately 50% of the mass is embedded in lipid bilayer (transmembrane domain) in 12 alpha-helic es (transmembrane helices; TMHs) and accommodates a water-filled chann el for substrate passage (glucose channel) whose tertiary structure is currently unknown. Using recent advances in protein structure predict ion algorithms we proposed here two three-dimensional structural model s for the transmembrane glucose channel of GLUT1 glucose transporter. Our models emphasize the physical dimension and water accessibility of the channel, loop lengths between TMHs, the macrodipole orientation i n four-helix bundle motif, and helix packing energy. Our models predic t that five TMHs, either TMHs 3, 4, 7, 8, 11 (Model 1) or TMHs 2, 5, 1 1, 8, 7 (Model 2), line the channel, and the remaining TMHs surround t hese channel-lining TMHs. We discuss how our models are compatible wit h the experimental data obtained with this protein, and how they can b e used in designing new biochemical and molecular biological experimen ts in elucidation of the structural basis of this important protein fu nction.